We are developing tissue culture model systems to elucidate the biologic characteristics of early abnormal proliferations in urothelium obtained from patients by transurethral resection. Specimens from 84 patients have been cultured in a three-dimensional matrix of collagen-coated cellulose sponge, and a variety of morphologic changes have been identified after one week of cultivation. To increase the breadth of our ability to subclassify lesions of similar histopathology, we have tried to cultivate clinical tumors in the meniscus-gradient model, where bladder carcinoma cell lines have shown distinctive zonal responses to the gradient of decreasing oxygen tension. We are now combining collagen-coated cellulose sponge and meniscus gradient principles, and early work is encouraging. As an additional tool for subclassification of clinical lesions we are developing a series of molecular probes using bladder cancer cell lines. Two chemicals under study are vitamin A and papaverine. BIBLIOGRAPHIC REFERENCES: Tchao, R., and Leighton, J. Inhibitory effect of dibutyryl cyclic AMP and theophylline on the aggregation of human breast tumor cell line BT-20. Nature, 259: 220-222, 1976. Tchao, R., Valentich, J.D., Rabitor, C.A., and Leighton, J. Studies on the regulation of transeptithelial fluid transport by a cell line: MDCK (abstract). In press IN VITRO. Invited paper at the Annual Meeting of the Tissue Culture Association, June, 1977.